Chapter 20: Carboxylic Acids and Nitriles شیمی آلی 2 Dr M. Mehrdad University of Guilan, Department of Chemistry, Rasht, Iran m-mehrdad@guilan.ac.ir Based on McMurry s Organic Chemistry, 7 th edition
The Importance of Carboxylic Acids (RCO 2 H) Abundant in nature from oxidation of aldehydes and alcohols in metabolism Acetic acid, CH 3 CO 2 H, - vinegar Butanoic acid, CH 3 CH 2 CH 2 CO 2 H (rancid butter) Long-chain aliphatic acids from the breakdown of fats Carboxylic acids present in many industrial processes and most biological processes An understanding of their properties and reactions is fundamental to understanding organic chemistry 2
The Importance of Carboxylic Acids (RCO 2 H) They are the starting materials from which other acyl derivatives are made 3
The Importance of Carboxylic Acids (RCO 2 H) They are the starting materials from which other acyl derivatives are made 4
20.1 Naming Carboxylic Acids & Nitriles Carboxylic Acids, RCO 2 H If derived from open-chain alkanes, replace the terminal -e of the alkane name with -oic acid The carboxyl carbon atom is C #1 5
20.1 Naming Carboxylic Acids & Nitriles Carboxylic Acids, RCO 2 H If derived from open-chain alkanes, replace the terminal -e of the alkane name with -oic acid The carboxyl carbon atom is C #1 Propanoic acid 4-Methylpentanoic acid 3-Ethyl-6-methyloctanedioic acid 6
Alternative Names Compounds with CO 2 H bonded to a ring are named using the suffix -carboxylic acid The CO 2 H carbon is not itself numbered in this system 7
Alternative Names Compounds with CO 2 H bonded to a ring are named using the suffix -carboxylic acid The CO 2 H carbon is not itself numbered in this system trans-4-hydroxycyclohexanecarboxylic acid 1-cyclopentenecarboxylic acid 8
Common Names: Carboxylic acids some of the 1st compound studied so some of their common names are still used. Especially for those with biological interest. Names accepted by IUPAC 9
Common Names: 10
Nitriles, RCN Closely related to carboxylic acids named by adding -nitrile as a suffix to the alkane name, with the nitrile carbon numbered C #1 4-Methylpentanenitrile 11
Nitriles, RCN Complex nitriles are named as derivatives of carboxylic acids. Replace -ic acid or -oic acid ending with onitrile or by replacing the carboxylic acid ending with -carbonitrile 12
Nitriles, RCN Complex nitriles are named as derivatives of carboxylic acids. Replace -ic acid or -oic acid ending with onitrile or by replacing the carboxylic acid ending with -carbonitrile Acetonitrile (From acetic acid) Benzonitrile (From benzoic acid) 2,2-Dimethylcyclohexanecarbonitrile (From 2,2-dimethylcyclohexanecarboxylic acid) 13
20.2 Structure & Properties Carboxyl carbon sp 2 hybridized: planar with bond angles of approximately 120 14
20.2 Structure & Properties: Carboxylic acids form hydrogen bonds, exist as cyclic dimers held together by 2 hydrogen bonds Strong hydrogen bonding causes much higher boiling points than the corresponding alcohols 1-Propanal (MW = 58) 1-Propanol (MW = 60) Ethanoic Acid (Acetic acid) MW = 60 CH 3 CH 2 CH 2 -OH Boiling Point 49 o C 97 o C 118 o C 15
Dissociation of Carboxylic Acids Carboxylic acids are proton donors toward weak and strong bases, producing metal carboxylate salts, RCO 2 + M Carboxylic acids with more than six carbons are only slightly soluble in water, but their conjugate base salts are water-soluble 16
Acidity Constant and pk a Carboxylic acids transfer a proton to water to give H 3 O + and carboxylate anions, RCO 2, but H 3 O + is a much stronger acid pk a = ~5 pk a = 15.7 (acts as a base here) pk a = -1.7 Lower pka means stronger acid so equilibrium favors starting materials The acidity constant, K a,, is about 10-5 carboxylic acid (pk a ~ 5) for a typical 17
Substituent Effects on Acidity Electron withdrawing (electronegative) substituents (like F, Cl, Br, I) promote formation of the carboxylate ion so raise the K a (lower the pk a ) The acidity constant, K a,, is about 10-5 for a typical carboxylic acid (pk a ~ 5) K a,, ~10-15 to -16 for alcohols and water (pk a ~ 15 to 16) CH 3 OH 15.5 H 2 O 15.7 18
Resonance Effects on Acidity Alcohols Phenols Carboxylic acid Inorganic acids 19
Resonance Effects on Acidity Alcohols weaker acids since O - not stabilized by resonance C=O Bond length (120 pm) C-O Bond length (134 pm) Negative charge spread over O-C-O C-O Bond lengths same (127 pm) Carboxylic acids more acidic since O - stabilized by resonance 20
20.3 Biological Acids and the Henderson-Hasselbalch Equation اسید های بیولوژیکی و معادله هندرسون- هاسل بالخ If pk a of given acid and the ph of the medium are known, % of dissociated and undissociated forms can be calculated using the Henderson-Hasselbalch eqn 21
20.4 Substituent Effects on Acidity Electron withdrawing (electronegative) substituents (like F, Cl, Br, I) promote formation of the carboxylate ion so raise the K a (lower the pk a ) They stabilize the carboxylate anion by induction 22
Aromatic Substituent Effects electron-donating (activating) group (like OCH 3 ) decreases acidity by destabilizing the carboxylate anion electron-withdrawing ( deactivating) groups (like -NO 2 ) increase acidity by stabilizing the carboxylate anion 23
Aromatic Substituent Effects 24
20.5 Preparation of Carboxylic Acids: From Oxidation of Benzylic Carbons Oxidation of a substituted alkylbenzene with KMnO 4 or Na 2 Cr 2 O 7 gives a substituted benzoic acid 1 and 2 alkyl groups can be oxidized, but 3 are not 1 o CH 2 CH 3 KMnO 4 H 3 C C CH CH 3 H 3 C CH3 CH 3 2 o 3 o 3 o O C H 3 C C C H 3 C CH3 O OH OH 25
From Oxidative Cleavage of Alkenes Oxidative cleavage of an alkene with KMnO 4 gives a carboxylic acid if the alkene has at least one vinylic hydrogen CH 3 CH 2 H KMnO 4 CH 3 CH 2 C C CH 3 CH 3 H 3 O + C O + O C CH 3 OH CH 3 CH 3 CH 2 H KMnO 4 CH 3 CH 2 C C H H H 3 O + C HO O + O C OH OH CO 2 26
From Oxidation of 1 o Alcohols & Aldehydes Oxidation of a 1 o alcohols or aldehydes with CrO 3 in aqueous acid 27
Hydrolysis of Nitriles Hot acid or base yields carboxylic acids CH 3 CH 2 CH 2 C N O H 3 O + or CH 3 CH 2 CH 2 C 1) NaOH 2) H 3 O + OH 28
Halides Nitriles Carboxylic Acids Conversion of an alkyl halide to a nitrile (by an S N 2 with cyanide ion) followed by hydrolysis produces a carboxylic acid with one more carbon (RBr RC N RCO 2 H) Best with 1 o halides because competing elimination reactions occur with 2 o or 3 o alkyl halides 29
Carboxylation of Grignard Reagents Grignard reagents react with dry CO 2 to yield a metal carboxylate Limited to alkyl halides that can form Grignard reagents The organomagnesium halide adds to C=O of carbon dioxide Protonation by addition of aqueous HCl in a separate step gives the free carboxylic acid 30
Halides Nitriles Carboxylic Acids Halides Grignard Carboxylic Acids 31
Carboxylic acid transfer a proton to a base to give anions, which are good nucleophiles in S N 2 reactions 20.6 Reactions of Carboxylic Acids: An Overview NaOH 1) LiAlH 4 2) H 3 O + Like ketones, carboxylic acids undergo addition of nucleophiles to the carbonyl group Carboxylic acids undergo substitutions reactions characteristic of neither alcohols nor ketones 32
20.7 Chemistry of Nitriles Nitriles and carboxylic acids both have a carbon atom with three bonds to an electronegative atom, and contain a bond C s of nitriles and carboxylic acids are electrophilic d+ d- d+ d- d- d+ 33
Preparation of Nitriles: Dehydration of Amides Reaction of primary amides RCONH 2 with SOCl 2 POCl 3 (or other dehydrating agents) Not limited by steric hindrance or side reactions (as is the reaction of alkyl halides with NaCN) or 34
Mechanism: Dehydration of Amides Nucleophilic amide oxygen atom attacks SOCl 2 followed by deprotonation and elimination Nucleophilic amide oxygen atom attacks SOCl 2 Deprotonation of acidic H on N Elimination of the SO 2 and Cl leaving groups 35
Reactions of Nitriles RC N is strongly polarized and with an electrophilic carbon Attacked by nucleophiles to yield sp 2 -hybridized imine anions 36
Hydrolysis: Nitriles Carboxylic Acids Hydrolyzed in with acid or base catalysis to a carboxylic acid and ammonia or an amine 37
Mechanism: Hydrolysis of Nitriles Nucleophilic addition of hydroxide to C N bond Protonation gives a hydroxy imine, which tautomerizes to an amide A second hydroxide adds to the amide carbonyl group and loss of a proton gives a dianion Expulsion of NH 2 gives the carboxylate 38
Mechanism: Step 4: Hydrolysis of Amides 39
Reduction: Nitriles 1 o Amines Reduction of a nitrile with LiAlH 4 gives a primary amine Nucleophilic addition of hydride ion (H-) to the polar C N bond, yields an imine anion The C=N bond undergoes a second nucleophilic addition of hydride (H-) to give a dianion, which is protonated by water 40
Reaction of Nitriles with Organometallic Reagents Grignard reagents add to give an intermediate imine anion that is hydrolyzed by addition of water to yield a ketone 41
Reactions of Nitriles: Overview 42
20.8 Spectroscopy of Carboxylic Acids and Nitriles Infrared Spectroscopy O H bond of the carboxyl group gives a very broad absorption 2500 to 3300 cm 1 C=O bond absorbs sharply between 1710 and 1760 cm 1 Free carboxyl groups absorb at 1760 cm 1 Commonly encountered dimeric carboxyl groups absorb in a broad band centered around 1710 cm 1 43
Infrared Spectroscopy O H bond of the carboxyl group gives a very broad absorption 2500 to 3300 cm 1 Commonly encountered dimeric carboxyl groups absorb in a broad band centered around 1710 cm 1 44
IR of Nitriles Nitriles show an intense C N bond absorption near 2250 cm 1 for saturated compounds and 2230 cm 1 for aromatic and conjugated molecules This is highly diagnostic for nitriles 45
C-13 NMR Carboxyl 13 COOH signals are at d165 to d185 Aromatic and,b-unsaturated acids are near d165 and saturated aliphatic acids are near d185 13 C N signal d115 to d130 46
Proton NMR The acidic CO 2 H proton is a singlet near d 12 When D 2 O is added to the sample the CO 2 H proton is replaced by D causing the absorption to disappear from the NMR spectrum 47